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Caroline Dive
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MS 15 - Molecular Testing (ID 537)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Biology/Pathology
- Presentations: 1
- Moderators:J.S. Lee, Iver Petersen
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 301 + 302
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MS 15.03 - Molecular Testing Using Blood (Liquid Biopsy) (ID 7713)
16:25 - 16:45 | Presenting Author(s): Caroline Dive
- Abstract
- Presentation
Abstract:
Tumour biopsies are the ‘gold standard’ with which to interrogate a patient’s tumour biology and assess biomarkers useful for treatment decision making. However, for longitudinal monitoring of disease in certain cancer types (e.g. lung) and particularly in patients with multiple metastatic lesions), serial biopsies may not be readily acquired and easily repeatable and a less invasive tumour sample is required. Liquid biopsies are beginning to gain acceptance as a surrogate for tumour profiling and in NSCLC, regulatory approval has been given for EGFR mutation testing in circulating tumour DNA (ctDNA) where biopsies are not available. My presentation will cover the development and utility of liquid biopsies in lung cancer, focusing on both ctDNA and circulating tumour cells (CTC). An avalanche of new technology platforms for circulating tumour cell (CTC) analysis is arriving in translational research laboratories, employing different approaches to CTC enrichment, purification and molecular characterisation. The semi-automated, robust and validated CellSearch platform (Menarini) remains the only technology that is FDA approved to determine patient prognosis (in breast, prostate, and colorectal cancers) by enumeration of EpCam expressing CTCs. CellSearch CTC count is also prognostic in both SCLC and NSCLC. The the ability to preserve CTCs for analysis 96h after blood draw is a major advantage for multicentre clinical trial scenarios. However, since CTCs are heterogenous and may downregulate epithelial markers during epithelial to mesenchyme transition (EMT) it is critical that marker independent CTC technologies are adopted to better explore CTC biology and heterogeneity, and the potential for a wider range of CTC based biomarkers is becoming apparent. I will review a range of CTC enrichment and isolation approaches and discuss our data on single CTC molecular profiling. I will compare and contrast the challenges for CTC profiling in small cell lung cancer (where EpCam positive CTCs are prevalent) and NSCLC (where EpCam positive CTCs are rare). I will also discuss the development of CTC patient-derived explant models (CDX) from SCLC and NSCLC patients and the advantages these may provide over conventional PDX models generated from a tissue biopsy. I will describe the utility of CDX models in drug development and in exploring the biology of progressing lung cancers, including vasculogeneic mimicry whereby SCLC cells adopt endothelial characteristics that may facilitate tumour growth and metastasis. I will present our ctDNA profiling approaches for selection of patients to early clinical trials and finally I will scan the horizon to the potential use of CTC and ctDNA as potential early detection biomarkers that complement CT scans. Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F, Li Y, Burt DJ, Antonello J, Morrow CJ, Hodgkinson CL, Morris K, Priest L, Carter M, Miller C, Hughes A, Blackhall F, Dive C, Brady G. Nat Med. 2017 Jan;23(1):114-119. Vasculogenic mimicry in small cell lung cancer. Williamson SC, Metcalf RL, Trapani F, Mohan S, Antonello J, Abbott B, Leong HS, Chester CP, Simms N, Polanski R, Nonaka D, Priest L, Fusi A, Carlsson F, Carlsson A, Hendrix MJ, Seftor RE, Seftor EA, Rothwell DG, Hughes A, Hicks J, Miller C, Kuhn P, Brady G, Simpson KL, Blackhall FH, Dive C. Nat Commun. 2016 Nov 9;7:13322. Circulating Tumor Cells Detected in the Tumor-Draining Pulmonary Vein Are Associated with Disease Recurrence after Surgical Resection of NSCLC. Crosbie PA, Shah R, Krysiak P, Zhou C, Morris K, Tugwood J, Booton R, Blackhall F, Dive C.J Thorac Oncol. 2016 Oct;11(10):1793-7. Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study. Morrow CJ, Trapani F, Metcalf RL, Bertolini G, Hodgkinson CL, Khandelwal G, Kelly P, Galvin M, Carter L, Simpson KL, Williamson S, Wirth C, Simms N, Frankliln L, Frese KK, Rothwell DG, Nonaka D, Miller CJ, Brady G, Blackhall FH, Dive C. Ann Oncol. 2016 Jun;27(6):1155-60. Genetic profiling of tumours using both circulating free DNA and circulating tumour cells isolated from the same preserved whole blood sample. Rothwell DG, Smith N, Morris D, Leong HS, Li Y, Hollebecque A, Ayub M, Carter L, Antonello J, Franklin L, Miller C, Blackhall F, Dive C, Brady G. Mol Oncol. 2016 Apr;10(4):566-74. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F, Polanski R, Burt DJ, Simpson KL, Morris K, Pepper SD, Nonaka D, Greystoke A, Kelly P, Bola B, Krebs MG, Antonello J, Ayub M, Faulkner S, Priest L, Carter L, Tate C, Miller CJ, Blackhall F, Brady G, Dive C. Nat Med. 2014 Aug;20(8):897-903. Molecular analysis of circulating tumour cells-biology and biomarkers. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C.Nat Rev Clin Oncol. 2014 Mar;11(3):129-44 Clinical utility of circulating tumour cell detection in non-small-cell lung cancer. Fusi A, Metcalf R, Krebs M, Dive C, Blackhall F. Curr Treat Options Oncol. 2013 Dec;14(4):610-22.
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